The major goal of the Perissi lab is to investigate the transcriptional and non-transcriptional functions of various cofactors with a particular focus on their misregulation during disease states such as cancer, diabetes and other inflammatory disorders. We have been interested for a long time in the regulation of transcriptional events by corepressor and coactivator complexes and in particular we have focused on the NCoR/SMRT corepressors and its associated proteins HDAC3, TBL1 and TBLR1. More recently, based on the finding that another component of the same complex, GPS2, was required for the adipogenic differentiation of 3T3-L1 cells, we began investigating the mechanism of its actions in adipogenesis and uncovered a critical, non-transcriptional role for GPS2 in regulating the enzymatic activity of the TRAF2/CIAP1/Ubc13 ubiquitin conjugating complex and therefore inhibiting the pro-inflammatory TNFalpha pathway. Our goal now is to investigate, both in vitro and in vivo, in tissue-specific mouse models, how the different components of the NCoR complex contribute to broadly regulate the cellular responses to external stimulation by acting in different cellular compartments to modulate hormonal and inflammatory pathways. Ongoing projects aim at: i) determining GPS2 role in the regulation of K63 ubiquitin chain formation within inflammatory responses regulated by Toll-like receptors and TNFalpha in macrophages and B-cells; ii) dissecting the molecular mechanism of GPS2 role in nuclear receptor-mediated transcriptional regulation in differentiating and mature adipocytes; iii) understanding how GPS2 sub-cellular localization and specific functions are regulated by post-translational modifications in different cell types.

Opportunities:

Please contact Dr. Perissi by e-mail for more information about open positions for postdoctoral fellows and graduate students.

Research Themes:

Metabolism, Obesity/Diabetes

Signal Transduction and Cancer

Self-Described Keywords

inflammation

nuclear receptors

transcription

ubiquitin

Publications

Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications.
Faculty can login to make corrections and additions.